The present invention relates to a method and an apparatus for generating a shockwave, a method for accelerating particles, a particle accelerating apparatus, a drug delivery apparatus, and/or a method and an apparatus for delivering DNA.
As molecular biology has recently discovered the cause of many diseases, the importance of gene therapy will expectedly still increase. The actual condition of arteriosclerosis is the inflammatory, hyperplastic reaction of the endothelium and/or smooth muscle of vessels against damage, and is considered to be a good application for the gene therapy. However, the delivery of DNA into cells requires virus vector, ribosome and others. With the usage of these means, infection and potential carcinogenesis are serious risk factors for the application of gene therapy. Also, low efficiency of the DNA delivery is an obstacle.
For instance, stable gene growth can be achieved with retrovirus, but the efficiency of the DNA is low and the risk of corcinogenesis cannot be avoided. Adenovirus delivers DNA at a higher efficiency rate, but immunoreaction and crytotoxicity is reportedly induced with this means, and the risk of delivering extraneous DNA to unintended organs has been pointed out. DNA delivery without using virus, on the other hand, may have less risk of toxicity but, due to the low efficiency and low growth level, this method has not been widely adapted. Therefore, a method to deliver DNA physically and precisely to the limited target tissue or organ in situ may well decrease the difficulties to a large extent.
The particle delivery system (PDS) with the use of a shockwave is a method to deliver DNA into cells which is attached to particles of gold or tungsten which is harmless to cells, which is then accelerated to a speed higher the the speed of sound by the shockwave to pierce through the cell membrane, thus causing the DNA to be delivered into the cells. Investigations both in vitro and in vivo have proved that the DNA growth is sustained for a long period of time. Thus, the PDS is considered to serve most suitably as a means of gene therapy.
Conventionally, the mainstream of the PDS has been such that a burst of the compressed helium or nitrogen generates a shockwave, and metallic micro particles are accelerated by the high speed airflow behind the shockwave.
However, when the conventional PDS is redirected and applied from intravitam, especially intravascular therapy, to gene therapy, problems will arise such as troublesome handling of compressed gas and the hindering large size of the apparatus console.
The present invention is directed to solving these problems with the conventional PDS wherein the purpose is to provide a new method for generating a shockwave which allows miniaturization, better maneuverability and higher reliability and an apparatus thereby, a method for accelerating particles and an apparatus thereby, an apparatus for delivering drugs, a method for delivering DNA and an apparatus thereby.
The inventors of the present invention have developed a totally new DNA delivery apparatus by means of laser ablation and researched primarily on the possibility of gene therapy using the apparatus to treat obstructive cerebrovascular disease.
It is a feature of the present invention that, in order to achieve the above mentioned object, in the method for generating a shockwave, a short pulse energy, which is absorbed and causes vaporization and plasmatization of the metal, is applied on a surface of the metal foil, such that a jet is generated by a sudden expansion of the metal gas and wherein a shockwave is generated on the surface of the other side of the metal foil.
It is a feature of the present invention that the shockwave generating apparatus comprises a metal foil and an energy source which discharges short pulse energy which is applied on a side of the metal foil, thus absorbed and causes vaporization and plasmatization of the metal.
The short pulse energy of the shockwave generating apparatus according to the present invention is preferably light energy including but not limited to laser light energy or electrical energy which induces electric discharge between the energy source and the metal foil.
The energy source of the shockwave generating apparatus according to the present invention can preferably adjust one or more elements of the short pulse energy such as pulse width, strength waveform, the amount of energy, and energy density of the short pulse energy.
The thickness of the metal foil according to the present invention is preferably unequal, i.e., has a variable thickness.
The method for generating a shockwave and/or the shockwave generating apparatus according to the present invention has a capability to adjust a characteristic of the shockwave to be generated by changing the thickness of the metal used and/or the material of the metal used.
It is a feature of the present invention that, in the method for accelerating particles, a short pulse energy, which is absorbed and causes vaporization and plasmatization of the metal, is applied on the surface of the side of the metal foil, such that a jet is generated by a sudden expansion of the metal gas and thus a shockwave is generated on the surface of the other side of the metal foil, which then accelerates the micro particles located on the surface of the other side of the metal foil.
In the method for accelerating particles according to the present invention, the micro particles are comprised, for example, of inorganic substances including but not limited to metal, sapphire, diamond, alumina and garnet.
With the method for accelerating particles according to the present invention, the micro particles may be comprised of solid drugs.
It is a feature of the present invention that the apparatus for accelerating particles comprises the shockwave generating apparatus and a designated area for the micro particles to accelerate on the surface of the other side of the metal foil where the short pulse energy is applied.
It is a feature of the present invention that the apparatus for delivering drugs comprises the shockwave generating apparatus and a designated area for the micro particles of solid drugs to deliver into organism on the surface of the other side of the metal foil where the short pulse energy is applied.
It is a feature of the present invention that, in the method for delivering DNA, a short pulse energy, which is absorbed and causes vaporization and plasmatization of a metal, is applied on the surface of a side of the metal foil, such that a jet is generated by a sudden expansion of the metal gas and thus a shockwave is generated on the surface of the other side of the metal foil, which then accelerates the micro particles carrying DNA located on the surface of the other side of the metal foil to deliver DNA into organism cells.
The method for delivering DNA according to the present invention preferably delivers the micro particles carrying DNA into human body cells with the capability of adjusting the depth of its travel.
It is a feature of the present invention that the apparatus for delivering DNA comprises the shockwave generating apparatus and a designated area for the micro particles carrying DNA on the surface of the other side of the metal foil where the short pulse energy is applied.
According to the present invention, short pulse energy such as Q-switch laser light irradiated to a metal foil induces dissolution and, as a result of its reaction, a shockwave is generated in the metal foil. The shockwave is reflected on the surface of the other side of the metal foil as an expanded wave, thus the metal foil is deformed instantaneously and the micro particle on the metal foil is blasted off at an extremely high speed. This principle is simple so that the method is applied to almost all the area of human body with the use of endoscopes, thus such that a flexible and variable introduction of gene therapy can be achieved.